During cardiac arrest, the surface electrocardiogram (ECG) can be used to assess the state of the myocardium. The scaling exponent (ScE) is a quantitative ECG descriptor of ventricular fibrillation (VF) waveform. The ScE correlates with the duration of VF, and is predictive of rescue shock outcome in both swine and humans. Furthermore, the therapies that alter the likelihood of resuscitation also affect the ScE. This proposal will examine the mechanisms that affect rescue shock outcome and the ScE using an established, clinically relevant porcine model of prolonged VF. We will examine the effects of high-energy phosphate (HEP) depletion, ischemia, sodium, calcium, and potassium channel regulation, reperfusion, acid-base status, and temperature. These studies are innovative in that they will use a clinically available indicator (the ScE) to guide resuscitation in a whole animal model that also allows examination of resuscitation outcomes. Our specific aims will be: 1) Define the relationships between myocardial metabolic state, changes in the VF waveform, and rescue shock outcome; 2) Define the relationships between alterations in ionic conductances, changes in the VF, and rescue shock outcome; 3) Identify a drug combination that optimally restores organization of VF, improves rescue shock outcomes, and stabilizes post-resuscitation hemodynamics. We will examine the effects of high-energy phosphate (HEP) depletion, ischemia, sodium, calcium, and potassium channel regulation, reperfusion, acid-base status, and temperature. These studies are novel because they will use a recently discovered, clinically available indicator (the ScE) in a model that will also allow examination of resuscitation outcomes.